Critical Care Bulletin: June 2023

 

Definitions of massive transfusion in adults with critical bleeding: a systematic review

 

by Victor S. Lin, Emily Sun, Serine Yau, Chathuri Abeyakoon, Georgia Seamer, Simran Bhopal, Harriet Tucker, Carolyn Doree, Susan J. Brunskill, Zoe K. McQuilten, Simon J. Stanworth, Erica M. Wood and Laura Green 

 

Critical Care volume 27, Article number: 265 Published: 05 July 2023

 

Background

Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.

Methods

We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.

Results

Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3–5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).

Conclusions

Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a ‘one-size-fits-all’ approach should be used across different clinical settings.

 

Extended prone positioning for intubated ARDS: a review

 

by Thaïs Walter and Jean-Damien Ricard 

 

Critical Care volume 27, Article number: 264 Published: 05 July 2023

 

During the COVID-19 pandemic, several centers had independently reported extending prone positioning beyond 24 h. Most of these centers reported maintaining patients in prone position until significant clinical improvement was achieved. One center reported extending prone positioning for organizational reasons relying on a predetermined fixed duration. A recent study argued that a clinically driven extension of prone positioning beyond 24 h could be associated with reduced mortality. On a patient level, the main benefit of extending prone positioning beyond 24 h is to maintain a more homogenous distribution of the gas–tissue ratio, thus delaying the increase in overdistention observed when patients are returned to the supine position. On an organizational level, extending prone positioning reduces the workload for both doctors and nurses, which might significantly enhance the quality of care in an epidemic. It might also reduce the incidence of accidental catheter and tracheal tube removal, thereby convincing intensive care units with low incidence of ARDS to prone patients more systematically. The main risk associated with extended prone positioning is an increased incidence of pressure injuries. Up until now, retrospective studies are reassuring, but prospective evaluation is needed.

 

A new reservoir-based CPAP with low oxygen consumption: the Bag-CPAP

 

by Eloïse de Beaufort, Guillaume Carteaux, François Morin, Arnaud Lesimple, Anne-Fleur Haudebourg, Emeline Fresnel, Damien Duval, Alexandre Broc, Alain Mercat, Laurent Brochard, Dominique Savary, François Beloncle, Armand Mekontso Dessap and Jean-Christophe Richard 

 

Critical Care volume 27, Article number: 262 Published: 04 July 2023

 

Background

Several noninvasive ventilatory supports rely in their design on high oxygen consumption which may precipitate oxygen shortage, as experienced during the COVID-19 pandemic. In this bench-to-bedside study, we assessed the performance of a new continuous positive airway pressure (CPAP) device integrating a large reservoir (“Bag-CPAP”) designed to minimize oxygen consumption, and compared it with other CPAP devices.

Methods

First, a bench study compared the performances of Bag-CPAP and four CPAP devices with an intensive care unit ventilator. Two FiO2 targets (40–60% and 80–100%) at a predefined positive end expiratory pressure (PEEP) level between 5 and 10 cm H2O were tested and fraction of inspired oxygen (FiO2) and oxygen consumption were measured. Device-imposed work of breathing (WOB) was also evaluated. Second, an observational clinical study evaluated the new CPAP in 20 adult patients with acute respiratory failure in two hospitals in France. Actual FiO2, PEEP, peripheral oxygen saturation, respiratory rate, and dyspnea score were assessed.

Results

All six systems tested in the bench study reached the minimal FiO2 target of 40% and four reached at least 80% FiO2 while maintaining PEEP in the predefined range. Device-delivered FiO2/consumed oxygen ratio was the highest with the new reservoir-based CPAP irrespective of FiO2 target. WOB induced by the device was higher with Bag-CPAP. In the clinical study, Bag-CPAP was well tolerated and could reach high (> 90%) and moderate (> 50%) FiO2 with an oxygen flow rate of 15 [15–16] and 8 [7–9] L/min, respectively. Dyspnea score improved significantly after introduction of Bag-CPAP, and SpO2 increased.

Conclusions

In vitro, Bag-CPAP exhibited the highest oxygen saving properties albeit had increased WOB. It was well accepted clinically and reduced dyspnea. Bag-CPAP may be useful to treat patients with acute respiratory failure in the field, especially when facing constraints in oxygen delivery.

 

Acute-on-chronic liver failure: far to go—a review

 

by Jinjin Luo, Jiaqi Li, Peng Li, Xi Liang, Hozeifa Mohamed Hassan, Richard Moreau and Jun Li 

 

Critical Care volume 27, Article number: 259 Published: 01 July 2023

 

Acute-on-chronic liver failure (ACLF) has been recognized as a severe clinical syndrome based on the acute deterioration of chronic liver disease and is characterized by organ failure and high short-term mortality. Heterogeneous definitions and diagnostic criteria for the clinical condition have been proposed in different geographic regions due to the differences in aetiologies and precipitating events. Several predictive and prognostic scores have been developed and validated to guide clinical management. The specific pathophysiology of ACLF remains uncertain and is mainly associated with an intense systemic inflammatory response and immune-metabolism disorder based on current evidence. For ACLF patients, standardization of the treatment paradigm is required for different disease stages that may provide targeted treatment strategies for individual needs.

 

Human-centered visualization technologies for patient monitoring are the future: a narrative review

 

by Greta Gasciauskaite, Justyna Lunkiewicz, Tadzio R. Roche, Donat R. Spahn, Christoph B. Nöthiger and David W. Tscholl 

 

Critical Care volume 27, Article number: 254 Published: 28 June 2023

 

Medical technology innovation has improved patient monitoring in perioperative and intensive care medicine and continuous improvement in the technology is now a central focus in this field. Because data density increases with the number of parameters captured by patient-monitoring devices, its interpretation has become more challenging. Therefore, it is necessary to support clinicians in managing information overload while improving their awareness and understanding about the patient’s health status. Patient monitoring has almost exclusively operated on the single-sensor–single-indicator principle—a technology-centered way of presenting data in which specific parameters are measured and displayed individually as separate numbers and waves. An alternative is user-centered medical visualization technology, which integrates multiple pieces of information (e.g., vital signs), derived from multiple sensors into a single indicator—an avatar-based visualization—that is a meaningful representation of the real-world situation. Data are presented as changing shapes, colors, and animation frequencies, which can be perceived, integrated, and interpreted much more efficiently than other formats (e.g., numbers). The beneficial effects of these technologies have been confirmed in computer-based simulation studies; visualization technologies improved clinicians’ situation awareness by helping them effectively perceive and verbalize the underlying medical issue, while improving diagnostic confidence and reducing workload. This review presents an overview of the scientific results and the evidence for the validity of these technologies.

 

ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies

 

Intensive Care Medicine published 16 June 2023

 

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of 

acute respiratory distress syndrome

 (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients’ representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.

 

Time to treatment and mortality for clinical sepsis subtypes

 

by Anne Yang, Jason N. Kennedy, Katherine M. Reitz, Gary Phillips, Kathleen M. Terry, Mitchell M. Levy, Derek C. Angus and Christopher W. Seymour 

 

Critical Care volume 27, Article number: 236 Published: 15 June 2023

 

Background

Sepsis is common, deadly, and heterogenous. Prior analyses of patients with sepsis and septic shock in New York State showed a risk-adjusted association between more rapid antibiotic administration and bundled care completion, but not an intravenous fluid bolus, with reduced in-hospital mortality. However, it is unknown if clinically identifiable sepsis subtypes modify these associations.

Methods

Secondary analysis of patients with sepsis and septic shock enrolled in the New York State Department of Health cohort from January 1, 2015 to December 31, 2016. Patients were classified as clinical sepsis subtypes (α, β, γ, δ-types) using the Sepsis ENdotyping in Emergency CAre (SENECA) approach. Exposure variables included time to 3-h sepsis bundle completion, antibiotic administration, and intravenous fluid bolus completion. Then logistic regression models evaluated the interaction between exposures, clinical sepsis subtypes, and in-hospital mortality.

Results

55,169 hospitalizations from 155 hospitals were included (34% α, 30% β, 19% γ, 17% δ). The α-subtype had the lowest (N = 1,905, 10%) and δ-subtype had the highest (N = 3,776, 41%) in-hospital mortality. Each hour to completion of the 3-h bundle (aOR, 1.04 [95%CI, 1.02–1.05]) and antibiotic initiation (aOR, 1.03 [95%CI, 1.02–1.04]) was associated with increased risk-adjusted in-hospital mortality. The association differed across subtypes (p-interactions < 0.05). For example, the outcome association for the time to completion of the 3-h bundle was greater in the δ-subtype (aOR, 1.07 [95%CI, 1.05–1.10]) compared to α-subtype (aOR, 1.02 [95%CI, 0.99–1.04]). Time to intravenous fluid bolus completion was not associated with risk-adjusted in-hospital mortality (aOR, 0.99 [95%CI, 0.97–1.01]) and did not differ among subtypes (p-interaction = 0.41).

Conclusion

Timely completion of a 3-h sepsis bundle and antibiotic initiation was associated with reduced risk-adjusted in-hospital mortality, an association modified by clinically identifiable sepsis subtype.

 

Tidal lung hysteresis to interpret PEEP-induced changes in compliance in ARDS patients

 

by Francesco Mojoli, Marco Pozzi, Eric Arisi, Silvia Mongodi, Anita Orlando, Giuseppe Maggio, Federico Capra Marzani and Laurent Brochard 

 

Critical Care volume 27, Article number: 233 Published: 13 June 2023

 

Background

In ARDS, the PEEP level associated with the best respiratory system compliance is often selected; however, intra-tidal recruitment can increase compliance, falsely suggesting improvement in baseline mechanics. Tidal lung hysteresis increases with intra-tidal recruitment and can help interpreting changes in compliance. This study aims to assess tidal recruitment in ARDS patients and to test a combined approach, based on tidal hysteresis and compliance, to interpret decremental PEEP trials.

Methods

A decremental PEEP trial was performed in 38 COVID-19 moderate to severe ARDS patients. At each step, we performed a low-flow inflation-deflation manoeuvre between PEEP and a constant plateau pressure, to measure tidal hysteresis and compliance.

Results

According to changes of tidal hysteresis, three typical patterns were observed: 10 (26%) patients showed consistently high tidal-recruitment, 12 (32%) consistently low tidal-recruitment and 16 (42%) displayed a biphasic pattern moving from low to high tidal-recruitment below a certain PEEP. Compliance increased after 82% of PEEP step decreases and this was associated to a large increase of tidal hysteresis in 44% of cases. Agreement between best compliance and combined approaches was accordingly poor (K = 0.024). The combined approach suggested to increase PEEP in high tidal-recruiters, mainly to keep PEEP constant in biphasic pattern and to decrease PEEP in low tidal-recruiters. PEEP based on the combined approach was associated with lower tidal hysteresis (92.7 ± 20.9 vs. 204.7 ± 110.0 mL; p < 0.001) and lower dissipated energy per breath (0.1 ± 0.1 vs. 0.4 ± 0.2 J; p < 0.001) compared to the best compliance approach. Tidal hysteresis ≥ 100 mL was highly predictive of tidal recruitment at next PEEP step reduction (AUC 0.97; p < 0.001).

Conclusions

Assessment of tidal hysteresis improves the interpretation of decremental PEEP trials and may help limiting tidal recruitment and energy dissipated into the respiratory system during mechanical ventilation of ARDS patients.

 

Influence of gender on age-associated in-hospital mortality in patients with sepsis and septic shock: a prospective nationwide multicenter cohort study

by Ryoung-Eun Ko, Danbee Kang, Juhee Cho, Soo Jin Na, Chi Ryang Chung, Sung Yoon Lim, Yeon Joo Lee, Sunghoon Park, Dong Kyu Oh, Su Yeon Lee, Mi Hyeon Park, Haein Lee, Chae-Man Lim and Gee Young Suh 

Critical Care volume 27, Article number: 229 Published: 11 June 2023

 

Background

Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group.

Methods

This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19–50 years, 50–80 years, and ≥ 80 years old individuals.

Results

During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02–1.29). Interestingly, in the age 19–50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35–0.93)]. For female, the risk of death remained relatively stable until around age 80 (P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 (P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19–50 groups (adjusted OR = 0.29, 95% CI = 0.12–0.69).

Conclusions

Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis.

 

 

 

 

 

Efficacy and Safety of Ciprofol Sedation in ICU Patients Undergoing Mechanical Ventilation: A Multicenter, Single-Blind, Randomized, Noninferiority Trial

 

by Liu, Yongjun; Peng, Zhiyong; Liu, Songqiao; Yu, Xiangyou; Zhu, Duming; Zhang, Linlin; Wen, Jianli; An, Youzhong; Zhan, Liying; Wang, Xiaochuang; Kang, Yan; Pan, Aijun; Yan, Jing; Zhang, Lina; Liu, Fengming; Zeng, Jun; Lin, Qinhan; Sun, Renhua; Yu, Jiangquan; Wang, Huaxue; Yao, Li; Chen, Chuanxi; Liu, Ning; Nie, Yao; Lyu, Jie; Wu, Kun; Wu, Jianfeng; Liu, Xiao; Guan, Xiangdong 

 

Critical Care Medicine - June 02, 2023

 

Objectives: 

To determine the effectiveness and safety of ciprofol for sedating patients in ICUs who required mechanical ventilation (MV).

Design: 

A multicenter, single-blind, randomized, noninferiority trial.

Setting: 

Twenty-one centers across China from December 2020 to June 2021.

Patients: 

A total of 135 ICU patients 18 to 80 years old with endotracheal intubation and undergoing MV, who were expected to require sedation for 6–24 hours.

Interventions: 

One hundred thirty-five ICU patients were randomly allocated into ciprofol (n = 90) and propofol (n = 45) groups in a 2:1 ratio. Ciprofol or propofol were IV infused at loading doses of 0.1 mg/kg or 0.5 mg/kg, respectively, over 4 minutes ± 30 seconds depending on the physical condition of each patient. Ciprofol or propofol were then immediately administered at an initial maintenance dose of 0.3 mg/kg/hr or 1.5 mg/kg/hr, to achieve the target sedation range of Richmond Agitation-Sedation Scale (+1 to –2). Besides, continuous IV remifentanil analgesia was administered (loading dose: 0.5–1 μg/kg, maintenance dose: 0.02–0.15 μg/kg/min).

Measurements and Main Results: 

Of the 135 patients enrolled, 129 completed the study. The primary endpoint-sedation success rates of ciprofol and propofol groups were 97.7% versus 97.8% in the full analysis set (FAS) and were both 100% in per-protocol set (PPS). The noninferiority margin was set as 8% and confirmed with a lower limit of two-sided 95% CI for the inter-group difference of –5.98% and –4.32% in the FAS and PPS groups. Patients who received ciprofol had a longer recovery time (p = 0.003), but there were no differences in the remaining secondary endpoints (all p > 0.05). The occurrence rates of treatment-emergent adverse events (TEAEs) or drug-related TEAEs were not significantly different between the groups (all p > 0.05).

Conclusions: 

Ciprofol was well tolerated, with a noninferior sedation profile to propofol in Chinese ICU patients undergoing MV for a period of 6–24 hours.

 

Mechanical ventilation in patients with acute brain injury: a systematic review with meta-analysis

 

by Karim Asehnoune, Paul Rooze, Chiara Robba, Marwan Bouras, Luciana Mascia, Raphaël Cinotti, Paolo Pelosi and Antoine Roquilly 

 

Critical Care volume 27, Article number: 221 Published: 06 June 2023

 

Objective

To describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation.

Design

Systematic review with an individual data meta-analysis.

Setting

Observational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt < 8 ml/Kg of IBW versus Vt >  = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) < or >  = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes.

Population

Patients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h.

Main outcome measures

The primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio.

Results

The meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p < 0.01).

Conclusions

Low tidal volume, moderate to high PEEP, or protective ventilation were not associated with mortality and lower incidence of ARDS in patients with acute brain injury undergoing invasive mechanical ventilation. However, protective ventilation improved oxygenation and could be safely considered in this setting. The exact role of ventilatory management on the outcome of patients with a severe brain injury needs to be more accurately delineated.